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Murepavadin
Murepavadin also known as POL7080 is a '' Pseudomonas'' specific peptidomimetic antibiotic. It is a synthetic cyclic beta hairpin peptidomimetic based on the cationic antimicrobial peptide protegrin I (PG-1) and the first example of an outer membrane protein-targeting antibiotic class with a novel, nonlytic mechanism of action, highly active and selective against the protein transporter LptD of '' Pseudomonas aeruginosa''. In preclinical studies the compound was highly active on a broad panel of clinical isolates including multi-drug resistant ''Pseudomonas '' bacteria with outstanding '' in vivo'' efficacy in sepsis, lung, and thigh infection models. Intravenous murepavadin is in development for the treatment of bacterial hospital-acquired pneumonia and bacterial ventilator-associated pneumonia due to ''Pseudomonas aeruginosa''. Discovery and structure The host defense antimicrobial peptide protegrin I (PG-1), exhibits broad-spectrum antimicrobial activity and good ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protegrin
Protegrins are small peptides containing 16-18 amino acid residues. Protegrins were first discovered in porcine leukocytes and were found to have antimicrobial activity against bacteria, fungi, and some enveloped viruses. The amino acid composition of protegrins contains six positively charged arginine residues and four cysteine residues. Their secondary structure is classified as cysteine-rich β-sheet antimicrobial peptides, AMPs, that display limited sequence similarity to certain defensins and tachyplesins. In solution, the peptides fold to form an anti-parallel β-strand with the structure stabilized by two cysteine bridges formed among the four cysteine residues. Recent studies suggest that protegrins can bind to lipopolysaccharide, a property that may help them to insert into the membranes of gram-negative bacteria and permeabilize them. Structure There are five known porcine protegrins, PG-1 to PG-5. Three were identified biochemically and rest of them were deduced from D ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pseudomonas
''Pseudomonas'' is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able to colonize a wide range of niches. Their ease of culture ''in vitro'' and availability of an increasing number of ''Pseudomonas'' strain genome sequences has made the genus an excellent focus for scientific research; the best studied species include ''P. aeruginosa'' in its role as an opportunistic human pathogen, the plant pathogen '' P. syringae'', the soil bacterium '' P. putida'', and the plant growth-promoting ''P. fluorescens, P. lini, P. migulae'', and ''P. graminis''. Because of their widespread occurrence in water and plant seeds such as dicots, the pseudomonads were observed early in the history of microbiology. The generic name ''Pseudomonas'' created for these organisms was defined in rather vague terms by Walter Migula i ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Structure–activity Relationship
The structure–activity relationship (SAR) is the relationship between the chemical structure of a molecule and its biological activity. This idea was first presented by Crum-Brown and Fraser in 1865. The analysis of SAR enables the determination of the chemical group responsible for evoking a target biological effect in the organism. This allows modification of the effect or the potency of a bioactive compound (typically a drug) by changing its chemical structure. Medicinal chemists use the techniques of chemical synthesis to insert new chemical groups into the biomedical compound and test the modifications for their biological effects. This method was refined to build mathematical relationships between the chemical structure and the biological activity, known as quantitative structure–activity relationships (QSAR). A related term is structure affinity relationship (SAFIR). Structure-biodegradability relationship The large number of synthetic organic chemicals currently in prod ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Antimicrobial Peptides
Antimicrobial peptides (AMPs), also called host defence peptides (HDPs) are part of the innate immune response found among all classes of life. Fundamental differences exist between prokaryotic and eukaryotic cells that may represent targets for antimicrobial peptides. These peptides are potent, broad spectrum antibiotics which demonstrate potential as novel therapeutic agents. Antimicrobial peptides have been demonstrated to kill Gram negative and Gram positive bacteria, enveloped viruses, fungi and even transformed or cancerous cells. Unlike the majority of conventional antibiotics it appears that antimicrobial peptides frequently destabilize biological membranes, can form transmembrane channels, and may also have the ability to enhance immunity by functioning as immunomodulators. Structure Antimicrobial peptides are a unique and diverse group of molecules, which are divided into subgroups on the basis of their amino acid composition and structure. Antimicrobial peptides are g ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Toxicology
Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating exposures to toxins and toxicants. The relationship between dose and its effects on the exposed organism is of high significance in toxicology. Factors that influence chemical toxicity include the dosage, duration of exposure (whether it is acute or chronic), route of exposure, species, age, sex, and environment. Toxicologists are experts on poisons and poisoning. There is a movement for evidence-based toxicology as part of the larger movement towards evidence-based practices. Toxicology is currently contributing to the field of cancer research, since some toxins can be used as drugs for killing tumor cells. One prime example of this is ribosome-inactivating proteins, tested in the treatment of leukemia. The word ''toxicology'' () is a neocla ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pharmacology
Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemical or physiological effect on the cell, tissue, organ, or organism (sometimes the word ''pharmacon'' is used as a term to encompass these endogenous and exogenous bioactive species). More specifically, it is the study of the interactions that occur between a living organism and chemicals that affect normal or abnormal biochemical function. If substances have medicinal properties, they are considered pharmaceuticals. The field encompasses drug composition and properties,functions,sources,synthesis and drug design, molecular and cellular mechanisms, organ/systems mechanisms, signal transduction/cellular communication, molecular diagnostics, interactions, chemical biology, therapy, and medical applications and antipathogenic capabilities. ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Pharmacokinetics
Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to determining the fate of substances administered to a living organism. The substances of interest include any chemical xenobiotic such as: pharmaceutical drugs, pesticides, food additives, cosmetics, etc. It attempts to analyze chemical metabolism and to discover the fate of a chemical from the moment that it is administered up to the point at which it is completely eliminated from the body. Pharmacokinetics is the study of how an organism affects a drug, whereas pharmacodynamics (PD) is the study of how the drug affects the organism. Both together influence dosing, benefit, and adverse effects, as seen in PK/PD models. Overview Pharmacokinetics describes how the body affects a specific xenobiotic/chemical after administration through the mechanisms of absorption and distribution, as ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gram-positive Bacteria
In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bacteria take up the crystal violet stain used in the test, and then appear to be purple-coloured when seen through an optical microscope. This is because the thick peptidoglycan layer in the bacterial cell wall retains the stain after it is washed away from the rest of the sample, in the decolorization stage of the test. Conversely, gram-negative bacteria cannot retain the violet stain after the decolorization step; alcohol used in this stage degrades the outer membrane of gram-negative cells, making the cell wall more porous and incapable of retaining the crystal violet stain. Their peptidoglycan layer is much thinner and sandwiched between an inner cell membrane and a bacterial outer membrane, causing them to take up the counterstain (sa ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Gram-negative Bacteria
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall sandwiched between an inner cytoplasmic cell membrane and a bacterial outer membrane. Gram-negative bacteria are found in virtually all environments on Earth that support life. The gram-negative bacteria include the model organism ''Escherichia coli'', as well as many pathogenic bacteria, such as ''Pseudomonas aeruginosa'', '' Chlamydia trachomatis'', and ''Yersinia pestis''. They are a significant medical challenge as their outer membrane protects them from many antibiotics (including penicillin), detergents that would normally damage the inner cell membrane, and lysozyme, an antimicrobial enzyme produced by animals that forms part of the innate immune system. Additionally, the outer leaflet of this membrane comprises a complex lipopol ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Colistin
Colistin, also known as polymyxin E, is an antibiotic medication used as a last-resort treatment for multidrug-resistant Gram-negative infections including pneumonia. These may involve bacteria such as ''Pseudomonas aeruginosa'', ''Klebsiella pneumoniae'', or ''Acinetobacter''. It comes in two forms: colistimethate sodium can be injected into a vein, injected into a muscle, or inhaled, and colistin sulfate is mainly applied to the skin or taken by mouth. Colistimethate sodium is a prodrug; it is produced by the reaction of colistin with formaldehyde and sodium bisulfite, which leads to the addition of a sulfomethyl group to the primary amines of colistin. Colistimethate sodium is less toxic than colistin when administered parenterally. In aqueous solutions it undergoes hydrolysis to form a complex mixture of partially sulfomethylated derivatives, as well as colistin. Resistance to colistin began to appear as of 2015. Common side effects of the injectable form include kidn ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Carbapenemase
Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems (ertapenem), although carbapenems are relatively resistant to beta-lactamase. Beta-lactamase provides antibiotic resistance by breaking the antibiotics' structure. These antibiotics all have a common element in their molecular structure: a four-atom ring known as a beta-lactam (β-lactam) ring. Through hydrolysis, the enzyme lactamase breaks the β-lactam ring open, deactivating the molecule's antibacterial properties. Beta-lactam antibiotics are typically used to target a broad spectrum of gram-positive and gram-negative bacteria. Beta-lactamases produced by gram-negative bacteria are usually secreted, especially when antibiotics are present in the environment. Structure The structure of a ''Streptomyces'' serine β-lactamase (SBLs) is given by . The alpha-beta fold ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Transport Protein
A transport protein (variously referred to as a transmembrane pump, transporter, escort protein, acid transport protein, cation transport protein, or anion transport protein) is a protein that serves the function of moving other materials within an organism. Transport proteins are vital to the growth and life of all living things. There are several different kinds of transport proteins. Carrier proteins are proteins involved in the movement of ions, small molecules, or macromolecules, such as another protein, across a biological membrane. Carrier proteins are integral membrane proteins; that is, they exist within and span the membrane across which they transport substances. The proteins may assist in the movement of substances by facilitated diffusion (i.e., passive transport) or active transport. These mechanisms of movement are known as carrier-mediated transport. Each carrier protein is designed to recognize only one substance or one group of very similar substances. Researc ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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